Abstract
Purpose
Bone marrow adherent cells contain conventional bone marrow stromal cells and mesenchymal stem cells and these cells constitute the hematopoietic microenvironment. Mesenchymal stem cells have the capacity to give rise to multiple mesenchymal lineage cells and even ectodermal lineage cells. In the present study, we investigated what types of tumor cells are inducible from BM adherent cells by chemical carcinogens.
Methods
Bone marrow cells from neonatal C3H/HeN mice were collected within 24 h after birth and then cultured. Four days later, bone marrow adherent cells were obtained and the cells were treated with 3-methylcholanthrene.
Results
By this treatment, some transformed clones consisting of large spindle cells were obtained. The transformed cells were highly positive for CD44 and were positive for Sca-1, CD49d and CD106, whereas the cells were negative for hematolymphoid markers. The cell clones had the ability to support hematopoiesis in vitro. These results indicate that the transformed cell lines have the characteristics of BM stromal cells/mesenchymal stem cells. Moreover, during culture of the transformed cells, spontaneous bone nodule formation was observed. When the transformed cells were inoculated into immunodeficient mice subcutaneously, the neoplasms grew in the subcutaneous tissue of the mice. Microscopically and ultrastructurally, the neoplasms showed the typical morphology of undifferentiated high-grade pleomorphic sarcoma (UHGPS). Bone-related genes have been found to be expressed in both transformed cells and UHGPSs.
Conclusion
The present study suggests that UHGPSs are derived from BM stromal cells, probably mesenchymal stem cells.
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Acknowledgments
Supported by a grant from the Haiteku Research Center of the Ministry of Education; a grant from the Millennium program of the Ministry of Education, Culture, Sports, Science and Technology; a grant from the Science Frontier program of the Ministry of Education, Culture, Sports, Science and Technology; a Grant-in-Aid for scientific research (B) 11470062; Grants-in-Aid for scientific research on priority areas (A) 10181225 and (A) 11162221, and Health and Labour Sciences research grants (Research on Human Genome, Tissue Engineering Food Biotechnology) and also a grant from the Department of Transplantation for Regeneration Therapy (Sponsored by Otsuka Pharmaceutical Company, Ltd.), a grant from Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd.; a grant from Japan Immunoresearch Laboratories Co., Ltd. (JIMRO). We thank Prof. Xiaohong Wang, MD., Department of Pathology, the 304th Hospital, PLA General Hospital, Beijing, China, and Hua Cao, M.D., Ph.D., Division of Medical Genetics, University of Washington, USA for kindly offering helpful information and advice. We also thank Ms. Y. Tokuyama, K. Hayasi and A. Kitajima for their expert technical assistance. We also thank Mr. Hilary Eastwick-Field and Ms. K. Ando for their help in the preparation of the manuscript. We declare that we have no conflict of interest.
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Li, Q., Hisha, H., Takaki, T. et al. Transformation potential of bone marrow stromal cells into undifferentiated high-grade pleomorphic sarcoma. J Cancer Res Clin Oncol 136, 829–838 (2010). https://doi.org/10.1007/s00432-009-0723-0
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DOI: https://doi.org/10.1007/s00432-009-0723-0